Core B Project Summary: The Goal of the Cellular Core (Core B) is to provide innovation and support to this Program Project to investigate HIV-1 Env antagonism in the context of the conformational states sampled by native HIV-1 Env. Core B will evaluate the impact of the small-molecule antagonists on sensitizing HIV-1-infected cells to antibody-dependent cellular cytotoxicity (ADCC). Core B will also help delineate the mechanisms of action of small-molecule Env inhibitors on trimeric Env expressed at the cell surface. Specifically, Core B will: (a) evaluate the ability of small- molecule Env entry inhibitors for their ability to sensitize HIV-1-infected cells to ADCC and (b) assess their impact on the conformation of functional Env trimers expressed on cell surfaces. Despite not being officially part of the Program Project in the most recent grant period, the Finzi laboratory has been a long-term collaborator and successfully interacted with Virology (Sodroski), Cyclic Peptides and Peptidomimetics (Chaiken), Small Molecule Synthesis (Smith), and Single Molecule FRET (Mothes) Projects to advance the understanding of Env conformational changes at the surface of infected cells, understand how Env conformations are modulated by different small-molecule antagonists generated by the Program Project and assess their impact on Env recognition and ADCC responses mediated by anti-Env antibodies and HIV+ sera.